The present invention is directed to various methods and devices for enhancing the implantation and differentiation of marrow-derived mesenchymal cells (i.e. mesenchymal stem cells).
Marrow-derived mesenchymal cells are the formative pluripotential blast cells found in the bone that are believed to be capable of differentiating into any of the specific types of connective tissues (i.e. the tissues of the body that support the specialized elements; particularly adipose, areolar, osseous, cartilaginous, elastic, and fibrous connective tissues) depending upon various environmental influences. Although these cells are normally present at very low frequencies in bone marrow, the inventors of the present invention have discovered a process for isolating, purifying, and greatly replicating the marrow-derived mesenchymal cells in culture, i.e. in vitro. This discovery is the subject of a co-pending U.S. patent application.
The present invention is directed to various devices and factors which have been developed in order to induce the culturally expanded marrow-derived mesenchymal cells to differentiate into specific types of desired phenotypes, such as bone or cartilage forming cells. For example, the inventors have found that various porous tri-calcium or hydroxyaptite ceramic devices can be utilized as vehicles or carriers for the culturally expanded marrow-derived mesenchymal cells when implanted into skeletal defects thereby permitting and/or promoting the differentiation of the cells into skeletal tissue.
Along this line, the inventors have discovered that certain factors, such as mechanical, cellular, and biochemical stimuli can be utilized in order to induce differentiation of the culturally expanded marrow-derived mesenchymal cells into bone forming cells, etc. Thus, the present invention provides for methods of utilizing the culturally expanded marrow-derived mesenchymal cells for correcting or modifying connective tissue disorders, such as the regeneration of missing or damaged skeletal tissue, enhancing the implantation of various plastic or metal prosthetic devices, etc., through the incorporation of the isolated and culturally expanded marrow-derived mesenchymal cells onto the porous surfaces of various tri-calcium or hydroxyaptite ceramic vehicles or carriers. Upon the activation and subsequent differentiation of the marrow-derived mesenchymal cells present in the porous ceramic vehicles or carriers, new connective tissues, such as natural viscous bridges, etc., can be generated.